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The genomes of outbred populations were first shown in 2006 to contain regions of homozygosity (ROHs) of several megabases. Further studies have also investigated the characteristics of ROHs in healthy individuals in various populations but there are no studies on Singapore populations to date. This study aims to identify and investigate the characteristics of ROHs in three Singapore populations. A total of 268 samples (96 Chinese, 89 Malays and 83 Indians) are genotyped on Illumina Human 1 M Beadchip and Affymetrix Genome-Wide Human SNP Array 6.0. We use the PennCNV algorithm to detect ROHs. We report an abundance of ROHs (≥500 kb), with an average of more than one hundred regions per individual. On average, the Indian population has the lowest number of ROHs and smallest total length of ROHs per individual compared with the Chinese and Malay populations. We further investigate the relationship between the occurrence of ROHs and haplotype frequency, regional linkage disequilibrium (LD) and positive selection. Based on the results of this data set, we find that the frequency of occurrence of ROHs is positively associated with haplotype frequency and regional LD. The majority of regions detected for recent positive selection and regions with differential LD between populations overlap with the ROH loci. When we consider both the location of the ROHs and the allelic form of the ROHs, we are able to separate the populations by principal component analysis, demonstrating that ROHs contain information on population structure and the demographic history of a population.

The abundance of copy number variants (CNVs) and regions of homozygosity (ROHs) have been well documented in previous studies. In addition, their roles in complex diseases and traits have since been increasingly appreciated. However, only a limited amount of CNV and ROH data is currently available for the Swedish population. We conducted a population-based study to detect and characterize CNVs and ROHs in 87 randomly selected healthy Swedish individuals using the Affymetrix SNP Array 6.0. More than 600 CNV loci were detected in the population using two different CNV-detection algorithms (PennCNV and Birdsuite). A total of 196 loci were consistently identified by both algorithms, suggesting their reliability. Numerous disease-associated and pharmacogenetics-related genes were found to be overlapping with common CNV loci such as CFHR1/R3, LCE3B/3C, UGT2B17 and GSTT1. Correlation analysis between copy number polymorphisms (CNPs) and genome-wide association studies-identified single-nucleotide polymorphisms also indicates the potential roles of several CNPs as causal variants for diseases and traits such as body mass index, Crohn's disease and multiple sclerosis. In addition, we also identified a total of 14 815 ROHs 500 kb or 2814 ROHs 1M in the Swedish individuals with an average of 170 and 32 regions detected per individual respectively. Approximately 141 Mb or 4.92% of the genome is homozygous in each individual of the Swedish population. This is the first population-based study to investigate the population characteristics of CNVs and ROHs in the Swedish population. This study found many CNV loci that warrant further investigation, and also highlighted the abundance and importance of investigating ROHs for their associations with complex diseases and traits.

Regions of homozygosity (ROHs) are more abundant in the human genome than previously thought. These regions are without heterozygosity, i.e. all the genetic variations within the regions have two identical alleles. At present there are no standardized criteria for defining the ROHs resulting in the different studies using their own criteria in the analysis of homozygosity. Compared to the era of genotyping microsatellite markers, the advent of high-density single nucleotide polymorphism genotyping arrays has provided an unparalleled opportunity to comprehensively detect these regions in the whole genome in different populations. Several studies have identified ROHs which were associated with complex phenotypes such as schizophrenia, late-onset of Alzheimer's disease and height. Collectively, these studies have conclusively shown the abundance of ROHs larger than 1 Mb in outbred populations. The homozygosity association approach holds great promise in identifying genetic susceptibility loci harboring recessive variants for complex diseases and traits.